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Total Synthesis of (−)‐Cephalotaxine and (−)‐Homoharringtonine via Furan Oxidation–Transannular Mannich Cyclization
Author(s) -
Ju Xuan,
Beaudry Christopher M.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201902174
Subject(s) - homoharringtonine , furan , chemistry , organic chemistry , combinatorial chemistry , medicinal chemistry , biology , leukemia , genetics
Homoharringtonine and its congener cephalotaxine were synthesized. Oxidative ring‐opening of a furan unveils an amine‐tethered dicarbonyl, which undergoes spontaneous transannular Mannich cyclization. The cascade builds the full cephalotaxine substructure in a single operation in 60 % yield. A Noyori reduction enabled synthesis of the title compounds with excellent enantioselectivity ( k rel =278).